protein protein interface, protein protein scoring, protein protein, protein-protein, PPI scoring

Protein-Protein Interface Scoring (Beta)

This panel scores bifunctional degrader ternary complexes by running multiple well-tempered metadynamics simulations and analysis. The job returns input structures with scores as a property. For metadynamics, all relevant files (metrics CSV, CMS, etc) are provided in the job directory.

To open this panel, do one of the following:

  • Click the Tasks button and browse to Biologics → Protein-Protein Interface Scoring (Beta)
  • Click the Tasks button and browse to Degraders and Macrocycles → Protein-Protein Interface Scoring (Beta)
  • Click the Tasks button and browse to Classical Simulation → Protein-Protein Interface Scoring (Beta)
  • Click the Tasks button and browse to Other Applications → Protein-Protein Interface Scoring (Beta)
  • Click the Tasks button and browse to Desmond → Protein-Protein Interface Scoring (Beta)
  • Features
  • Additional Resources

Protein-Protein Interface Scoring Panel Features

 

Input Poses

    Get from menu

    Use the menu to select a source to input poses: From File using the Browse button, or from the Project Table using the Load button after the first pose is included and atoms are selected. A text notification will appear when complete, as Pose imported or Pose included.
    All protein-protein poses must be conformers of the same two proteins, optionally in complex with their ligands (warheads). The output of the Generate Degrader Ternary Complexes Panel (Beta) may be used. If a file is specified, the first pose will be imported into the Maestro Project. If the input file has less than two structures, a warning message will be displayed.
PP Interface

    Chain set menus

    Use the menus to define the protein-protein interface. If the input poses are from a pose viewer file, the labels to define the protein-protein interfaces will appear as Protein 1 and Protein 2. If the input file is complex, the labels will be identified with Chain Set 1 and Chain Set 2. An error message will appear if residue selections within the same chain are made.
System Setup
    Box shape menu

    Select either Cubic or Orthorhombic.

    Box size field

    Enter a value in the field to define the buffer distance (in Å) for the box size.

    Force field menu

    Choose either OPLS5 or OPLS4 from the menu.

    Use customized version option
    Check the box to enable the use OPLS custom parameters. Click the orange icon on the right to open the Set Custom Parameters Location Dialog Box.
Method
Currently, only the Metadynamics method is available.
With Metadynamics method selected:
    Residues for CV options

    Select between 2 and 4 residues from each of the two binding sites, defined as Residue groups 1 and 2, set by their corresponding Load Selected buttons.

    Metadynamics Parameters

    Enter values into the fields to set the parameters for Width, Height, Wall, and Interval.

    The default values for the parameters for Width = 0.05, Height = 0.02, Wall = 35.00, and Interval = 0.12

    Simulation options

    Use the arrow buttons to adjust the number of Replicas per pose.

    Time (in nanoseconds) can be set by entering a value in the field.

Job Settings
Click the Gear icon to open the Protein-Protein Interface Scoring Job Settings.

Tutorials

Related Topics